2Points to PonderWhat is the genotype and the phenotype of an individual?What are the genotypes for a homozygous recessive and dominant individuals and a heterozygote individual?Be able to draw a punnett square for any cross (1-trait cross, 2-trait cross and a sex-linked cross).What are Tay-Sachs disease, Huntington disease, sickle-cell disease, and PKU?How are each of the above inherited?What is polygenic inheritance?What is a multifactorial trait?What is sex-linked inheritance?Name 3 X-linked recessive disorders.What is codominance?What is incomplete dominance?What do you think about genetic profiling?
3These traits are genetically inherited Genotype and phenotypeThese traits are genetically inheritedAnswer these questions about your inheritance:Do you have a widow’s peak?Are your earlobes attached or unattached?Do you have short or long fingers?Do you have freckles?Can you roll your tongue?Do you have Hitchhiker’s thumb?
4Some genetic vocabulary Gene: the basic unit of heredity in a living organism. A section of a chromosome that codes for a trait, or characteristic.Alleles: alternate forms of a specific gene at the same position (locus) on a gene (e.g. allele for unattached earlobes and attached lobes); alleles occur in pairs
5Genotype and phenotype Dominant allele: will be expressed and will mask a recessive allele (Tt or TT)Recessive allele: allele that is only expressed when a gene has two of this type of alleleHomozygous dominant genotype: 2 dominant alleles (TT or AA)Homozygous recessive genotype: 2 recessive alleles (tt or aa)Heterozygous genotype: one dominant allele and one recessive allele (Tt or Aa)
6Genotype and phenotype Genotype – specific genes for a particular trait written with symbolsPhenotype – the physical or outward expression of the genotypeGenotype PhenotypeEE unattached earlobeEe unattached earlobeee attached earlobeWhat are your genotype and phenotype?
8Gregor MendelDocumented a particulate mechanism of inheritance through his experiments with garden peasFigure 14.1
9“particulate” inheritance Parents pass on discrete heritable units, “genes” (Mendel referred to these as “factors”)
10Mendel’s experimentsConcept 14.1: Mendel used the scientific approach to identify some basic laws of inheritanceMendel discovered the basic principles of heredity by breeding garden peas in carefully planned and executed experiments
11Mendel’s Experimental, Quantitative Approach Mendel chose to work with peasBecause they are available in many varietiesBecause he could strictly control which plants mated with which
12Mendel’s experiments : Controls Wisely, Mendel chose to track only those characters that varied in an “either-or” manner: - dominant or recessive, no blended characteristics, no polygenic traitsMendel also made sure that:He started his experiments with varieties that were “true-breeding” (purebred lines isolated through self-pollination)
13In a typical breeding experiment Mendel mated two contrasting, true-breeding varieties, a process called hybridizationThe true-breeding parents are called the P generationThe hybrid offspring of the P generation are called the F1 generationWhen F1 individuals self-pollinate, the F2 generation is produced
14ALL of the offspring were purple. Why? The Law of SegregationWhen Mendel crossed contrasting, true-breeding white and purple flowered pea plantsALL of the offspring were purple. Why?
15Useful Genetic Vocabulary An organism that is homozygous for a particular geneHas a pair of identical alleles for that gene (ex: PP or pp)Exhibits true-breedingAn organism that is heterozygous for a particular gene (example: Pp)Has a pair of alleles that are different for that gene (hybrid)
16…but when Mendel crossed the F1 plants: Many of the F2 plants had purple flowers, but some had white flowersHe found a repeatable ratio of about three to one, purple to white flowers, in the F2 generationP Generation(true-breedingparents)PurpleflowersWhiteF1 Generation(hybrids)All plants hadpurple flowersF2 GenerationEXPERIMENT True-breeding purple-flowered pea plants andwhite-flowered pea plants were crossed (symbolized by ). Theresulting F1 hybrids were allowed to self-pollinate or were cross-pollinated with other F1 hybrids. Flower color was then observedin the F2 generation.RESULTS Both purple-flowered plants and white-flowered plants appeared in the F2 generation. In Mendel’sexperiment, 705 plants had purple flowers, and 224 had whiteflowers, a ratio of about 3 purple : 1 white.Figure 14.3
17Mendel’s “Factors” (genes) Mendel reasoned thatIn the F1 plants, only the purple flower “factor“ was affecting flower color in these hybridsPurple flower color was dominant, and white flower color was recessiveIn such cases, the dominant allele MASKS the recessive
18Mendel observed the same pattern in many other pea plant characters Mendel developed a hypothesis to explain the 3:1 inheritance pattern that he observed among the F2 offspringFour related concepts make up this model…Table 14.1
19First, alternative versions of genes AllelesFirst, alternative versions of genesAccount for variations in inherited characters, which are now called allelesFigure 14.4Allele for purple flowersLocus for flower-color geneHomologouspair ofchromosomesAllele for white flowers
20Second, for each character An organism inherits two alleles, one from each parentA genetic locus is actually represented twiceHomologous chromosomes, one paternal, one maternal Figure 14.4Allele for purple flowersLocus for flower-color geneHomologouspair ofchromosomesAllele for white flowers
21Dominants and Recessives Third, if the two alleles at a locus differThen one, the dominant allele, determines the organism’s appearanceThe other allele, the recessive allele, has no noticeable effect on the organism’s appearance (is “masked”)
22Vocabulary reviewAllele: different forms of a gene (for a trait). Homozygous: purebred; identical set of alleles for a trait Heterozygous: hybrid; nonmatching alleles
23Segregation principle Fourth, the law of segregationThe two alleles for a heritable character separate (segregate) during gamete formation and end up in different gametes
24Punnett SquaresDoes Mendel’s segregation model account for the 3:1 ratio he observed in the F2 generation of his numerous crosses?The Punnett square is a diagram that is used to predict an outcome of a particular cross or breeding experiment. It is named after Reginald C. Punnett, who devised the approach, and is used by biologists to determine the probability of an offspring having a particular genotype.
26Phenotypic ratio approximately 9:3:3:1 A dihybrid crossIllustrates the inheritance of two charactersProduces four phenotypes in the F2 generationYYRRP GenerationGametesYRyryyrrYyRrHypothesis ofdependentassortmentindependentF2 Generation(predictedoffspring)1⁄21 ⁄23 ⁄41 ⁄4SpermEggsPhenotypic ratio 3:1YryR9 ⁄163 ⁄161 ⁄16YYRrYyRRYyrrYYrryyRRyyRrPhenotypic ratio 9:3:3:131510810132Phenotypic ratio approximately 9:3:3:1F1 GenerationRESULTSCONCLUSION The results support the hypothesis of independent assortment. The alleles for seed color and seed shape sort into gametes independently of each other.EXPERIMENT Two true-breeding pea plants— one with yellow-round seeds and the other with green-wrinkled seeds—were crossed, producing dihybrid F1 plants. Self-pollination of the F1 dihybrids, which are heterozygous for both characters, produced the F2 generation. The two hypotheses predict different phenotypic ratios. Note that yellow color (Y) and round shape (R) are dominant.Figure 14.8
27Independent Assortment Principle Using the information from a dihybrid cross, Mendel developed the law of independent assortmentEach pair of alleles segregates independently during gamete formationAnimated version:
28The reality of inheritance Concept 14.3: Inheritance patterns are often more complex than predicted by simple Mendelian geneticsThe relationship between genotype and phenotype is rarely simpleWhat about green eyes? Hazel eyes?
29Extending Mendelian Genetics for a Single Gene The inheritance of characters by a single geneMay deviate from simple Mendelian patternsExceptions to the “rules” are listed in the following slidesNeed practice? Try these “drag and drop” Punnett squares
30The extent of variation Not only does meiosis guarantee segregation and independent assortment of alleles, but crossing over also mixes up alleles on homologous chromosomes before distribution“Therefore, in humans with 23 pairs of chromosomes, a gamete (egg or sperm) could have 223 or 8,388,604 possible combinations of chromosomes from that parent. Any couple could have 223 × 223 or 70,368,744,177,644 (70 trillion) different possible children, based just on the number of chromosomes, not considering the actual genes on those chromosomes.Thus, the chance of two siblings being exactly identical would be 1 in 70 trillion.In addition, something called crossing over, in which the two homologous chromosomes of a pair exchange equal segments during synapsis in Meiosis I, can add further variation to an individual’s genetic make-up.”
31Crossing over prior to gamete formation increases variables Sex and variationCrossing over prior to gamete formation increases variablesIndependent assortmentCrossover animation
32The Spectrum of Dominance Complete dominanceOccurs when the phenotypes of the heterozygote and dominant homozygote are identicalPPppPp
33Incomplete dominance Example: Flower colors RR = red R’R’ = white The phenotype of F1 hybrids is somewhere between the phenotypes of the two parental varietiesP GenerationF1 GenerationF2 GenerationRedCRCRGametesCRCWWhiteCWCWPinkCRCWSpermCw1⁄2EggsCR CRCR CWCW CWExample: Flower colorsRR = redR’R’ = whiteRR’ = pink (intermediate pigmentation)Figure 14.10
34The Spectrum of Dominance In codominanceTwo dominant alleles affect the phenotype in separate, distinguishable waysIAIB = The human blood group type AB is an example of codominanceRW = roan coat color in cattle or horses
35Multiple Alleles and Codominance Most genes exist in populationsIn more than two allelic formsTable 14.2The ABO blood group in humansIs determined by multiple alleles
36Frequency of Dominant Alleles Are not necessarily more common in populations than recessive allelesIt really depends on whether a trait gives an individual an adaptive advantage, and is naturally selected.Examples: type O blood (ii) recessive present in majority of population
37PleiotropyPleiotropy describes the genetic effect of a single gene on multiple phenotypic traits.The underlying mechanism is that the gene codes for a product that is, for example, used by various cells, or has a signaling function on various targets.A classic example of pleiotropy is the human disease PKU (phenylketonuria).This disease can cause mental retardation and reduced hair and skin pigmentation, and can be caused by any of a large number of mutations in a single gene that codes for the enzyme (phenylalanine hydroxylase), which converts the amino acid phenylalanine to tyrosine, another amino acid.Depending on the mutation involved, this results in reduced or zero conversion of phenylalanine to tyrosine, and phenylalanine concentrations increase to toxic levels, causing damage at several locations in the body.PKU is totally benign if a diet free from phenylalanine is maintained.
38Which of Mendel’s Laws does this defy? See linkage animation Gene LinkageSometimes, when genes are located close together on the same chromosome, they tend to be inherited together.Which of Mendel’s Laws does this defy?See linkage animationA “classic” example of this is why cats with white fur and blue eyes are (more often than not) also deaf.
39Extending Mendelian Genetics for Two or More Genes Many traits (especially in complex organisms)May be determined by two or more genes (polygenic)In EPISTASIS “standing upon”the phenomenon where the effects of one gene are modified by one or several other genes (which are sometimes called modifier genes).A gene at one locus alters the phenotypic expression of a gene at a second locus
40An example of epistasis in mice Here we see the effect the bb gene combo has on the C gene for the agouti (brownish) fur color in micecc combo = white furC_ combo = black fur,unless bb “stands upon” it. Then you get agouti color.BCbCBcbc1⁄4BBCcBbCcBBccBbccbbccbbCcBbCCbbCCBBCC9⁄163⁄164⁄16SpermEggsFigure 14.11
41Other variations in gene expression Incomplete Expressivity is seen in cases where individuals with the same genotypes may have, often for unknown reasons, variability in their phenotypes.This is often seen in genetic diseases where one person with a disease such as diabetes may be very severely effected while another with the same allele may have a milder form of the disease.Incomplete Penetrance is seen when an individual with a particular genotype does not express the phenotype. Again the reasons for this are not clearly understood.For example, known mutations in the gene responsible for Huntington disease have “95% penetrance”, because 5% of those with the dominant allele for Huntington disease don't develop the disease and 95% do.
42Beyond simple inheritance Polygenic traits - two or more sets of alleles govern one traitEach dominant allele codes for a product so these effects are additiveResults in a continuous variation of phenotypese.g. skin color ranges from very dark to very lightNote that: Environmental effects can cause intervening phenotypes!AaBbCcaabbccAabbccAaBbccAABbCcAABBCcAABBCC20⁄6415⁄646⁄641⁄64Fraction of progeny
43Polygenic inheritance Multifactorial trait – a trait that is influenced by both genetic and environmental factorse.g. skin color is influenced by sun exposuree.g. height can be affected by nutritionmostarethisheightNumber of Menfewfew62646668707274shorttallHeight in InchesCourtesy University of Connecticut/Peter Morenus, photographer;
44Genes are affected by Environment While there is a strong genetic component in human height, the average height has increased over the past 50 years in developed countries. This is considered to be due to improved nutrition.Likewise, a cotton plant may have the alleles necessary for high yields but if it doesn't receive enough water or fertilizer it cannot reach its genetic potential.
45Example:A phenotypic range of a particular genotype may be influenced by the environmentFigure 14.13Exact color often mirrors the pH of the soil; acidic soils produce blue flowers, neutral soils produce very pale cream petals, and alkaline soils results in pink or purple. This is caused by a color change of the flower pigments in the presence of aluminum ions which can be taken up into the flower.
47Humans are not convenient subjects for genetic research. Why? Many human charactersVary in the population along a continuum and are called “quantitative characters”Humans are not convenient subjects for genetic research. Why?However, the study of human genetics continues to advance
48A pedigreeIs a family tree that describes the interrelationships of parents and children across generationsInheritance patterns of particular traits can be traced and described using pedigreesWwwwWWorFirst generation(grandparents)Second generation(parents plus auntsand uncles)Thirdgeneration(two sisters)FfffFF or FfFFWidow’s peakNo Widow’s peakAttached earlobeFree earlobe(a) Dominant trait (widow’s peak)(b) Recessive trait (attached earlobe)
49Pedigree AnalysisHuman geneticists illustrate the inheritance of a gene within a family by using a pedigree chart. On such a chart, males are symbolized by a square ( □ ) and females are symbolized by a circle ( ○ ). People who are affected by a disease are symbolized by a dark circle or square.The pedigree chart below shows inheritance of the gene that causes albinism. A and B represent a couple who had five children, including C and E. Only one of the children, E, was albino. E and her husband had five children, including G. In the pedigree below write the genotypes of the individuals who are labeled with letters, using (A) to represent the dominant allele and (a) to represent the recessive allele. Start by indicating the genotypes of E and F. Then use a Punnett Square to figure out what the genotypes for C and D must be. Next, determine the genotypes of A and B. Finally, determine the genotype of G.
50Types of Gene Mutations Point mutations: caused by single-base substitution
51Sickle-Cell Disease Affects one out of 400 African-Americans Is caused by the substitution of a single amino acid in the hemoglobin protein in red blood cells(shows seven out of the 146 amino acid units of normal hemoglobin)
52Electrophoresis of the hemoglobin protein shows: We see that homozygous normal people have one type of hemoglobin (A) and anemics have type S, which moves more slowly in the electric field. The heterozygotes have both types, A and S. In other words, there is codominance at the molecular level.Try this pedigree of familial inheritance of SC disease
53Sickle Cell DiseaseHomozygous recessive individuals have sickle cell diseaseHeterozygous individuals are normal, but exhibit a mild version of the disease; said to “carry the trait” for SCHomozygous dominant individuals are normal.Genotypes:
54Sickle CellSymptoms include physical weakness, pain, organ damage, and even paralysisSickle-cell disease occurs more commonly in people (or their descendants) from parts of the world such as sub-Saharan Africa, where malaria is or was common, but it also occurs in people of other ethnicities. This is because those with one or two alleles of the sickle cell disease are resistant to malaria since the red blood cells are not conducive to the parasites - in areas where malaria is common there is a survival value in carrying the sickle cell genes.
55Review: Types of Gene Mutations Frame shift mutation: caused by insertion or deletion of a base; usually serious because they throw off the codon “reading frame”Result: protein is nonfunctional
56Recessively Inherited Autosomal Disorders Many genetic disordersAre inherited in a recessive manner (aa)So, most affected individuals are homozygous (dual inheritance)AA, Aa are normal phenotype, in this caseRecessively inherited disordersShow up only in individuals homozygous for the alleleCarriersAre heterozygous individuals who carry the recessive allele but are phenotypically normal
57Symptoms of cystic fibrosis include Mucus buildup in the some internal organsAbnormal absorption of nutrients in the small intestineLung tissue from a cystic fibrosis patient, showing extensive destruction as a result of obstruction and infection.H2OCl -nebulizerdefectivechannelpercussionvestthick mucus
58PhenyketonuriaPKU is an autosomal recessive genetic disorder that is characterized by an inability of the body to utilize the essential amino acid, phenylalanine. Amino acids are the building blocks for body proteins.In 'classic PKU', the enzyme (phenylalanine hydroxylase), that breaks down phenylalanine is completely or nearly completely deficient.This enzyme normally converts phenylalanine to another amino acid, tyrosine. Without this enzyme, phenylalanine and its' breakdown chemicals from other enzyme routes, accumulate in the blood and body tissues.Infants are born “normal” but if not treated, severe brain problems, such as mental retardation and seizures, will occur.Thus, this disease is GREATLY influenced by environmental factors
59Other autosomal recessive disorders Tay-Sachs diseaseAlbinismHemochromatosis types 1-3: the most common genetic disease in Europe.You can watch this animation:
60Dominantly Inherited Disorders Some human disordersAre due to dominant alleles One example is achondroplasiaA form of dwarfism that is lethal when homozygous for the dominant allele (DD)Figure 14.15
61Dominant allele Huntington’s disease Is a degenerative disease of the nervous systemHas no obvious phenotypic effects until about 35 to 40 years of ageLake Maracaibo, VenezuelaVillage pedigree
62X-linked disorders Sex-linked inheritance More often found in males than females because recessive alleles are always expressedMost X-linked disorders are recessive:Color blindness: most often characterized by red-green color blindnessDuchenne’s muscular dystrophy (DMD): characterized by wasting of muscles and death by age 20Fragile X syndrome: most common cause of inherited mental impairmentHemophilia: characterized by the absence of particular clotting factors that causes blood to clot very slowly or not at all
66Multifactorial Disorders Many human diseasesHave both genetic and environment componentsExamples includeHeart disease and cancerTry this interactive family pedigree (nicotine addiction)
67Genetic Testing and Counseling Genetic counselorsCan provide information to prospective parents concerned about a family history for a specific disease
68Counseling Based on Mendelian Genetics and Probability Rules Using family historiesGenetic counselors help couples determine the odds that their children will have genetic disorders
69Tests for Identifying Carriers For a growing number of diseasesTests are available that identify carriers and help define the odds more accuratelyFetal TestingIn amniocentesisThe liquid that bathes the fetus is removed and testedIn chorionic villus sampling (CVS)A sample of the placenta is removed and tested
71Concept: Some inheritance patterns are exceptions to the standard chromosome theory EpigeneticsFunctional modifications to the genome that do not involve a change in the nucleotide sequence.Environmental factors can alter the way our genes are expressed, making even identical twins different.Examples of such modifications are DNA methylation and histone modification, both of which serve to regulate gene expression without altering the underlying DNA sequence.
72Genomic Imprinting What Is Imprinting? For most genes, we inherit two working copies -- one from mom and one from dad. But with imprinted genes, we inherit only one working copy. Depending on the gene, either the copy from mom or the copy from dad is epigenetically silenced. Silencing usually happens through the addition of methyl groups during egg or sperm formation. The epigenetic tags on imprinted genes usually stay put for the life of the organism. But they are reset during egg and sperm formation. Regardless of whether they came from mom or dad, certain genes are always silenced in the egg, and others are always silenced in the sperm.
73(a) A wild-type mouse is homozygous for the normal igf2 allele. Genomic imprintingInvolves the silencing of certain genes that are “stamped” with an imprint during gamete productionIn mammals the phenotypic effects of certain genes depend on which allele is inherited from the mother and which is inherited from the father(a) A wild-type mouse is homozygous for the normal igf2 allele.Normal Igf2 allele(expressed)with imprint(not expressed)PaternalchromosomeMaternalWild-type mouse(normal size)Mutant lgf2 alleleDwarf mouseNormal size mouseWhen a normal Igf2 allele is inherited from the father, heterozygous mice grow to normal size But when a mutant allele is inherited from the father, heterozygous mice have the dwarf phenotype.
74Genes located outside the nucleus also have influence Extranuclear genesAre genes found in organelles in the cytoplasmThe inheritance of traits controlled by genes present in the chloroplasts (ctDNA) or mitochondria (mtDNA)Depends solely on the maternal parent because the zygote’s cytoplasm comes from the eggFigure 15.18
75In Humans:Some diseases affecting the muscular and nervous systems are caused by defects in mitochondrial genes that prevent cells from making enough ATPExamples of mitochondrial DNA diseases:Leber's hereditary optic atrophy - causes progressive visual impairmentKearns-Sayre diseaseProgressive external ophthalmoplegiaMyoclonus epilepsyMELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes)Mitomap - A human mitochondrial genome database